Randomized, controlled trial comparing S-1 with UFT/LV as adjuvant therapy for curatively resected stage III colorectal cancer (BCOG-CC02 study).

Abstract

520 Background: Oral anticancer drug, UFT/LV, has recently been reported to improve both overall survival (OS) and relapse free survival (RFS) for patients with Stage III colorectal cancer in Japan. We conducted a randomized clinical trial to compare S-1 with UFT/LV for adjuvant therapy in patients with Stage III colorectal cancer. Methods: Patients with Stage III colorectal cancer (PS, 0 to 1; age, 20 to 80 years) were randomized to take either UFT / LV (28 days per 5 weeks) for 6 months. or S-1 (28 days per 6 weeks) for 12 months started within 6 weeks following curative resection. We investigated the correlations between disease- free survival (DFS) and tissue mRNA levels of 5-FU and folate metabolism-related enzymes. In addition, we investigated overall survival (OS) and safety. Results: Between April 2008 and August 2010, a total of 145 patients were registered from 22 centers. There were no clear intergroup differences in background factors. The patients who relapsed during protocol duration of treatment were excluded, the percentages of patients who took expected dosage of medicine were 67.1% (47/70) and 87.3% (62/71) in S-1 and UFT/LV groups, respectively. Grade3 to 4 myelosuppression(4%), bilirubin(3%) and diarrhea(8%) were occurred in S-1 group whereas, grade 3 liver dysfunction (5%) and diarrhea (5%) occurred in UFT/LV group, but all of them were reversible. The median follow-up period was 934 days, 3-years’ DFS in patients of S-1 and UFT/LV groups were 65.9% and 72.7%, respectively (p=0.88). In a univariate analysis, topoisomerase-1 (TOPO-1) mRNA level was shown as a factor of the recurrences. A poor-prognosis patient population was observed in the S-1 group such as with low gamma-glutamyl hydrolase (GGH) mRNA level. Conclusions: Oral anticancer drug, S-1 showed an equivalent effect for UFT/LV in Stage III colorectal cancer as adjuvant therapy. Tissue levels of mRNA of 5-FU/ folate metabolism-related enzymes were important parameters for postoperative prognosis in patients with stage III colorectal cancer who take oral 5-FU derivatives for adjuvant therapy. Clinical trial information: UMIN000001560.